Association of IL‐37 gene polymorphisms with susceptibility to tuberculosis in Saudi subjects

Tuberculosis (TB) is one of the most common infectious diseases worldwide. IL‐37, a novel member of the IL‐1 family, has anti‐inflammatory activity. Various cytokine genes polymorphisms are reportedly associated with susceptibility to TB infection. However, an association between genetic variations in the IL‐37 gene and susceptibility to TB infection has not been investigated. The aim of this case‐control study was therefore to identify such an association in Saudi subjects, in which five single‐nucleotide polymorphisms (SNPs) in the IL‐37 gene were assessed. Serum concentrations of IL‐37 were evaluated using ELISA, and genetic variants genotyped by multiplex PCR and ligase detection reaction. It was found that the C/C genotype of rs2723176 (–6962 A/C) occurs significantly more frequently in patients with active TB and that the C allele of this SNP is associated with TB. In addition, the C allele of rs2723176 SNP was associated with high circulating concentrations of IL‐37. However, the genotype and allele frequency of the other four SNPs (rs3811046, rs3811047, rs2723186 and rs2723187) were not significantly associated with TB infection. In conclusion, the present data suggest that rs2723176 SNP of IL‐37 is involved in the development of TB infection. Furthermore, high circulating concentrations of IL‐37 may have a negative effect on protective immunity against TB infection.     

Variable impact transportation (VIT) model for energy and environmental impact of hauling truck operation

Purpose

Fuel economy and emissions of heavy-duty trucks greatly vary based on vehicular/environmental conditions. Large-scale infrastructure construction projects require a large amount of material/equipment transportation. Single-parameter generic hauling models may not be the best option for an accurate estimation of hauling contribution in life cycle assessment (LCA) involving construction projects; therefore, more precise data and parameterized models are required to represent this contribution. This paper discusses key environmental/operational variables and their impact on transportation of materials and equipment; a variable-impact transportation (VIT) model accounting for these variables was developed to predict environmental impacts of hauling.

Methods

The VIT model in the form of multi-nonlinear regression equations was developed based on simulations using the U.S. Environmental Protection Agency (EPA)’s Motor Vehicle Emission Simulator (MOVES) to compute all the impact categories in EPA’s TRACI 2.1 and energy consumption of transportation. Considering actual driving cycles of hauling trucks recorded during a pavement rehabilitation project, the corresponding environmental impacts were calculated, and sensitivity analyses were performed. In addition, an LCA case study based on historical pavement reconstruction projects in Illinois was conducted to analyze the contribution of transportation and variability of its impacts during the pavements’ life cycle.

Results and discussion

The importance of vehicle driving cycles was realized from simulation results. The case study results showed that considering driving cycles using the VIT model could increase the contribution of hauling in total life cycle Global Warming Potential (GWP) and total life cycle GWP itself by 2–4 and 3–5%, respectively. In addition to GWP, ranges of other hauling-related impact categories including Smog, Ozone Depletion, Acidification, and Primary Energy Demand from fuel were presented based on the case study. Ozone Depletion ranged from 9 to 45%, and Smog ranged from 11 to 48% of the total relevant life cycle impacts. The GWP contribution of hauling in pavement LCA ranged between 5 and 32%. The results indicate that the contribution of hauling transportation can be significant in pavement LCA.

Conclusions

For large-scale roadway infrastructure construction projects that need a massive amount of material transportation, high fidelity models and data should be used especially for comparative LCAs that can be used as part of decision making between alternatives. The VIT model provides a simple analytical platform to include the critical vehicular/operational variables without any dependence on an external software; the model can also be incorporated in those studies where some of the transportation activity data are available.

     

Environmental and economic impact of using new-generation wide-base tires

Purpose

New-generation wide-base tire (NG-WBT) is known for improving fuel economy and at the same time for potentially causing a greater damage to pavement. No study has been conducted to evaluate the net environmental saving of the combined system of pavements and NG-WBT. This study adopted a holistic approach (life cycle assessment [LCA] and life cycle costing [LCC]) to quantitatively evaluate the environmental and economic impact of using NG-WBT.

Methods

The net effect of different levels of market penetration of NG-WBT on energy consumption, global warming potential (GWP), and cost based on the fatigue cracking and rutting performance of two different asphalt concrete (AC) pavement structures was evaluated. The performance of pavements was determined based on pavement design lives; pavement surface characteristics, and pavement critical strain responses obtained from the artificial neural network (ANN) based on finite element (FE) simulations were used to calculate design lives of pavements. Based on the calculated design lives, life cycle inventory (LCI) and cost databases, and rolling resistance (RR) models previously developed by the University of Illinois at Urbana-Champaign (UIUC) were used to calculate the environmental and economic impact of the combined system.

Results and discussion

The fuel economy improvement using NG-WBT is 1.5% per axle. Scenario-based case studies were conducted. Considering 0% NG-WBT market penetration (or 100% standard dual tire assembly [DTA]) as a baseline, scenario 1 assumed the same fatigue and rutting potential between NG-WBT and DTA; therefore, the only difference came from fuel economy improvement of using NG-WBT. In scenario 2, pavement fatigue cracking potential determined the pavement design life; both thick and thin AC overlay sections experienced positive net environmental savings, but mixed net economic savings. In scenario 3, pavement rutting potential determined the pavement design life; the thick AC overlay section experienced positive net environmental savings, but mixed net economic savings. The thin section experienced negative net environmental and economic savings.

Conclusions

The outcomes of scenario-based case studies indicated that NG-WBT can result in significant savings in life cycle energy consumption and cost, and GWP; however, these benefits were sensitive to the method used to determine the pavement performance; especially, a small change in pavement strain can result in significant change in pavement life. In addition, the effect of fuel price/economy improvement, discount rate, and International Roughness Index (IRI) threshold values was studied in the sensitivity analyses.

     

Natural compounds of Palestine flora. Comparison analysis by static headspace and steam distillation GC-MS of semivolatile secondary metabolites from leaves of cultivated Palestinian Majorana syriaca

BACKGROUND: A comparative analysis by using static headspace (HS) and steam distillation (SD) GC-MS of the volatile and the semi-volatile secondary metabolites from leaves of cultivated Majorana syriaca. METHODS: The essential oils endogenous to cultivated thyme were isolated and identified by HS-GC-MS technology and compared to those from SD-GC-MS. RESULTS: The HS-GC-MS results showed that the Palestinian cultivated thyme is rich in monoterpene hydrocarbons and phenolic monoterpenes such as alpha-phellandrene, alpha-pinene, beta-myrcene, m-cymene, p-cymene, gamma-terpinene, thymol and carvacrol. In all the samples gamma-terpinene, p-cymene, thymol and carvacrol were the most abundant compounds. CONCLUSIONS: HS and SD-GC-MS have proved that most of the cultivated thyme samples examined has thymol isomer as the major phenolic constituent.     

Solvent-induced lysozyme gels: effects of system composition and temperature on structural and dynamic characteristics

The gelation process of lysozyme in water/tetramethylurea in the presence of salt was investigated as a function of temperature and system composition by rheology, infrared spectroscopy, and microcalorimetry. Times and temperatures of gelation were determined from the variation of the storage (G') and loss (G') moduli. It was found that gelation times follow exponential decays with both protein and tetramethylurea (TMU) concentrations and with temperature. The activation energy for the overall process shows a linear dependence on TMU mass fraction. A strongly increased beta-sheet content and reduced alpha-helix occur with the increase of TMU concentration in the binary solvent. Also, a linear decrease of lysozyme denaturation temperature and enthalpy on TMU concentration is found for the TMU mass fraction up to 0.5, above which no denaturation signal can be detected.     

Inhibition of P-glycoprotein-mediated multidrug efflux by aminomethylene and ketomethylene analogs of reversins

Several aminomethylene analogs and a ketomethylene analog of reversins were synthesized in order to evaluate their ability to inhibit P-glycoprotein-mediated drug efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein. These analogs retained good activity compared to cyclosporin A and the original reversins.     

Homing of annexin-labeled stem cells to apoptotic cells

Ischemic diseases are characterized by the presence of pro-apoptotic stimuli, which initiate a cascade of processes that lead to cell injury and death. Several molecules and events represent detectable indicators of the different stages of apoptosis. Among these indicators is phosphatidylserine (PS) translocation from the inner to the outer leaflet of the plasma membrane, which can be detected by annexinV (ANXA5) conjugation. This is a widely used in vivo and in vitro assay marking the early stages of apoptosis. We report here on an original method that employs PS-ANXA5 conjugation to target stem cells to apoptotic cells. Mesenchymal stem cells (MSCs) from GFP-positive transgenic rats were biotinylated on membrane surfaces with sulfosuccinimidyl-6-(biotinamido) hexanoate (sulfo-NHS-LC-biot) and then bound to avidin. The avidin-biotinylated MSCs were labeled with biotin conjugated ANXA5. Bovine aortic endothelial cells (BAE-1 cells) were exposed to UVC to induce caspasedependent apoptosis. Finally, we tested the ability of ANXA5-labeled MSCs to bind BAE-1 apoptotic cells: suspended ANXA5-labeled MSCs were seeded for 1 hour on a monolayer of UV-treated or control BAE-1 cells. After washing, the number of MSCs bound to BAE-1 cells was evaluated by confocal microscopy. Statistical analysis demonstrated a significant increase in the number of MSCs tagged to apoptotic BAE-1 cells. Therefore, stem cell ANXA5 tagging via biotin-avidin bridges could be a straightforward method of improving homing to apoptotic tissues. A. Gerasimou, R. Ramella and A. Brero contributed equally to this paper.     

Structure-activity relationship of natural and synthetic coumarins inhibiting the multidrug transporter P-glycoprotein

A set of 32 natural and synthetic coumarins were tested in order to evaluate their activity on human leukemic cells (K562/R7) overexpressing P-glycoprotein (P-gp). Their ability to reduce the P-gp-mediated drug efflux of daunorubicin out of cells was evaluated at 10 microM. Four natural compounds, previously isolated from Calophyllum dispar (Clusiaceae) and substituted by a common alpha-(hydroxyisopropyl)dihydrofuran moiety, exhibited a significant inhibitory effect on P-gp when compared to the positive control cyclosporin A. A 3D-quantitative structure-activity relationship (3D-QSAR) analysis of the coumarins was performed using the biological results obtained by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of P-gp. Results showed a favorable electrostatic and steric volume, like the alpha-(hydroxyisopropyl)dihydrofuran moiety, beside C(5)-C(6) or C(7)-C(8) positions. In addition, the analysis revealed an important hydrophobic, neutral charge group, like phenyl, in position C(4) on the coumarinic ring.     

Efficiency of IRAP and ITS-RFLP marker systems in accessing genetic variation of Pyrenophora graminea

The usefulness of IRAP (inter-retrotransposon amplified polymorphism) and ITS-RFLP (restriction of PCR-amplified internal transcribed spacers of the rDNA) markers in the analysis of 39 Pyrenophora graminea isolates was determined. Each marker system could discriminate between all of the isolates in detecting polymorphism, albeit with variable efficiency. IRAP and ITS-RFLP produced 85% and 77% polymorphic bands, respectively, with a corresponding mean polymorphic information content (PIC) of 0.38 and 0.36. The IRAP marker index ratio (2.41) was higher than ITS-RFLP (1.50). On one hand, the quality nature of data (QND) was higher for ITS-RFLP (0.169) than IRAP (0.093). However, correlation between both marker similarity matrices was significant (r = 0.34, p < 0.05). These findings suggest their combined use in phylogenetic analysis. To our knowledge, this is the first report of a comparison involving these two advanced DNA marker systems.     

Neuroanatomical study of the A11 diencephalospinal pathway in the non-human primate

Background

The A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it is thought to be involved in numerous painful conditions such as restless legs syndrome and migraine. Its anatomical organization, however, remains largely unknown in the non-human primate (NHP). We therefore characterized the anatomy of this pathway in the NHP.

Methods and Findings

In situ hybridization of spinal dopamine receptors showed that D1 receptor mRNA is absent while D2 and D5 receptor mRNAs are mainly expressed in the dorsal horn and D3 receptor mRNA in both the dorsal and ventral horns. Unilateral injections of the retrograde tracer Fluoro-Gold (FG) into the cervical spinal enlargement labeled A11 hypothalamic neurons quasi-exclusively among dopamine areas. Detailed immunohistochemical analysis suggested that these FG-labeled A11 neurons are tyrosine hydroxylase-positive but dopa-decarboxylase and dopamine transporter-negative, suggestive of a L-DOPAergic nucleus. Stereological cell count of A11 neurons revealed that this group is composed by 4002±501 neurons per side. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication with subsequent development of a parkinsonian syndrome produced a 50% neuronal cell loss in the A11 group.

Conclusion

The diencephalic A11 area could be the major source of L-DOPA in the NHP spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells.